Pharmacologically, the non-steroidal anti-inflammatory drugs (NSAIDs) act by inhibiting an enzyme, cyclooxygenase (COX), and hence the production of prostaglandins that follows from its activity.
COX exists in humans in 2 main isoforms that are involved in different processes. Type 1 cyclooxygenase (COX-1) is notably involved in the physiological process of gastric protection whereas type 2 cyclooxygenase (COX-2) is principally involved in the inflammatory process.
Generally, the conventional, non-selective NSAIDs inhibit both COX-1 and COX-2. In consequence, their use is associated with undesirable side-effects, notably including gastrointestinal lesions, which result directly from inhibition of COX-1.
This has led to the development of selective inhibitors of type 2 cyclooxygenase (COX-2), comprising the drug (or therapeutic) class of the COXIBs, for which the gastrointestinal effects are significantly reduced relative to non-selective NSAIDs (Moore et al. (2006) BMC Musculoskeletal Disorders 7:79-91). The main indications of COXIBs are for joint pains. We may mention, as examples, celecoxib (Celebrex®), parecoxib (Dynastat®), valdecoxib (Bextra®), rofecoxib (Vioxx®), etoricoxib (Arcoxia®), or lumiracoxib (Prexige®).
However, one of the main side-effects of the COXIBs is the development of cardiovascular disorders (see for example Caldwell et al. (2006) J. R. Soc. Med. 99:132-140). Accordingly, at present, valdecoxib and rofecoxib have been withdrawn from the market and certain countries have refused to grant marketing authorization for parecoxib. Moreover, lumiracoxib has also been refused marketing authorization because of the liver damage that it would cause.
It would therefore be important to be able to benefit from the therapeutic advantages offered by the COXIBs while limiting their side-effects.
Nefopam is the active principle of Acupan®. It is a non-opioid central analgesic in the benzoxazocine class (Klohs et al. (1972) Arzneimittelforschung 22:132-3). Its advantages notably include absence of respiratory depressant effects. Its mode of action is still poorly understood but seems to involve inhibition of monoamine reuptake, which distinguishes it from paracetamol and the non-steroidal anti-inflammatory drugs (NSAIDs). At present, nefopam is mainly used for treating postoperative pain. Thus, in France it is administered to about 20% of patients having undergone surgery (Fletcher et al. (2008) Pain 137:441-51).
